Noviembre 12, 2019

First human gene editing performed on human embryo

03 Agosto 2017, 09:27 | Faron Santos

Newly fertilized eggs before gene editing and embryos after gene editing and a few rounds of cell division. Courtesy OHSU Mitalipov lab

Newly fertilized eggs and embryos after gene editing

This gives parents full control over whether or not their child will carry a disease-associated gene, making it incorrect to think of genome editing in embryos as the only way to prevent genetic disease in kids.

These are valid points, but they don't change the fact that CRISPR-based genome editing offers not only the potential to remove defective genes but also add more desirable ones, which embryo screening does not.

But since it is possible to use preimplantation genetic diagnosis to test if in vitro fertilization embryos are carrying heterozygous mutations, Mitalipov's research would not appear to pass this threshold. They seem to have a knack when it comes to manipulating embryos.

Once the gene was removed, the embryo's own fix systems replaced them with the healthy version. The scientists made the gene edits early in the embryos' development and saw the efficiency of DNA correction go up.

The National Academy of Sciences released a report past year urging caution when using CRISPR to permanently alter inherited genes - exactly the thing done by the new study. The authors of the new study argue that their technique could be used to increase the proportion of embryos that lack potentially harmful genes. "Our expectation was that this was how embryos would respond". On the other hand, it highlights ethical dilemmas that we regularly grapple with in reproductive health. "And we need more basic research like this before we can even consider going forward". They edited them using CRISPR-Cas9 to correct the mutation. If you inherit the glitch, you have a 50% chance of passing it along to your children. Several days later, 72% of the embryos showed no sign of the mutated gene; the gene was essentially corrected in all of their cells.

The technique would need to approach 100% effectiveness to be ready for clinical trials aimed at producing pregnancies, Mitalipov said.

"We still have a long road ahead", Mitalipov said, before ever doing this in a human baby.

"One thing clear at this stage is that we shouldn't apply this technology in any shape or form toward designer babies", Wu said.

Mitalipov says he believes gene editing could be used as a preventive tool to lower a newborn's lifetime risk of a wide range of diseases, including cancer.

"It's a correction: We have not modified anything", Mitalipov said.

Robin Lovell-Badge, group leader at the Francis Crick Institute in London, said the fact that the embryos did not use the external DNA means new methods must be developed to permit efficient DNA template-directed fix.

"This genetic mutation is one of the most common causes of cardiomyopathy", Amato says.

"This paper is not announcing the dawn of the designer baby era", says R. Alta Charo, a lawyer and bioethicist at the University of Wisconsin Law School in Madison. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy.

In 2015, scientists in China conducted the first known attempt to use CRISPR on human embryos.

Doctors and medical researchers have demonstrated that genome modification can be highly effective at treating and preventing otherwise lethal and permanent human diseases.

Greely pointed out that the applications for this technology are actually pretty narrow.

In a series of laboratory experiments reported in the journal Nature, the OR researchers tried a different approach.

Normally cells will fix a CRISPR-induced cut in DNA by essentially gluing the ends back together.

"I don't want to be negative with our own discoveries, but it is important to inform the public of what this means", he said. Currently, the United States Congress has barred the U.S. Food and Drug Administration (FDA) from considering clinical trials involving germline engineering and the National Institutes of Health (NIH) is prohibited from funding gene-editing research in human embryos.

Still, the experiment moves the idea of tinkering with genes before birth "from future fantasy to the world of possibility", said Peter Braude, an emeritus professor of obstetrics and gynecology at King's College London.

Building on previous research from other groups, in the new research Ma and colleagues improve the success rates of DNA editing by changing the timing.

But HCM is only one of more than 10,000 known heritable disorders that are caused by a single gene - many of which could potentially be stopped by editing the relevant genes in embryos during IVF treatment as more is learnt about them in the future, scientists said.

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